1. Field of the Invention
The examination of isolated cells or clumps of cells obtained by scraping or washing cut surfaces of tissues or mucous membranes has long proved a useful device in pathological examinations. Early detection of cervical cancer, achieved in part through screening of women with cytologic examination of a cervical Papanicolaou-type (PAP) smear, has contributed significantly to the major improvements in the management of this cancer during the last 30 years. Papanicolaou studied the cytologic examination of cervical smears in the 1940's and extended his initial observations in the early diagnosis of cancer of the human uterine cervix to many fields of cancer diagnosis.
Although the magnitude of benefit is controversial, it appears clear that routine screening of women at risk using the PAP smear is effective in preventing the invasive form of cervical cancer and mortality from it. The PAP smear has changed little since 1943 when Papanicolaou and Trout reported that the cellular changes that accompany malignant tumors of the female genital tract can be used in the early detection of cervical cancer. In the technique, a spatula is used to scrape the cervix, and the resulting exfoliated cells are smeared onto a microscope slide. These cells are stained using several staining steps, and then the exfoliated cells are examined for the presence of abnormal cells by a specially trained cytotechnologist. Examination of a single slide may take up to fifteen minutes. The cellular changes may clearly indicate a cancer or, more likely, may indicate abnormalities that may be due to early stages of a cancer or to inflammation due to some other cause such as an infection. The cellular changes associated with the early stages of cancer are the most difficult to interpret. For this reason it must also be emphasized that there should be careful correlation between the use of the PAP smear and classical biopsy methods.
The field of exfoliative cytology has been extended beyond vaginal, cervical, and endometrial uterine smears to bronchial and prostatic secretions, gastric and colonic washings, impressions of the surface of tumors or the cut surface of biopsy specimens, especially lymph nodes, and serous fluids.
Bronchial secretions such as sputum may be an important specimen for early detection of lung cancer. Lung cancer accounts for more than 25% of all cancer deaths, is the leading cause of cancer deaths in men and is becoming an increasingly serious problem in women. The incidence of lung cancer is increasing very rapidly, with an increase of sixfold over the last forty years. All of the factors that are suspected to contribute to the increased incidence of lung cancer are expected to continue to be a part of modern life so that early detection and effective treatment of lung cancer are essential if there is to be an impact on the mortality due to this disease. Only about 5% of lung cancer patients are cured. The low cure rate is due to a number of factors, a primary factor being that the cancer is often too widespread at the time of its diagnosis to be effectively treated. Most lung cancers are diagnosed on the basis of clinical symptoms such as cough, dyspnea (difficulty in breathing), chest pain, hemoptysis (blood in the sputum), and wheezing. Lung cancers are detected by physical examination, chest x-ray, or exfoliative cytology from a sputum specimen. The use of sputum cytology for early detection of lung cancer is controversial, and the American Cancer Society guidelines for early cancer detection do not recommend sputum cytology. However, other authorities believe that sputum cytology may be a method of early cancer detection. Many lung cancer patients shed cells that demonstrate increasing degrees of cytologic abnormality for long periods of time before the detection of obvious cancer. This disagreement as to the usefulness of sputum cytology is probably due to the lack of well-controlled studies, to variations in the preparation of the specimens for cytologic examination, and to variations in the interpretation of the cytologic changes.
2. Description of the Prior Art
A monoclonal antibody against human basal cells which affects the growth of epidermal cells in vitro is disclosed by Oseroff, et al., in Clin. Res., 30:601A, 1982. Selective enrichment of human epidermal cell subpopulations using monoclonal antibodies is reported by Morhenn, et al., in J. Inv. Derm., 81:127s-131s, 1983.